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Elemental microanalysis of biological specimens.

Although X-ray microanalysis in the electron microscope is the most common method for microanalysis of biological specimens, other methods of elemental microanalysis (electron energy loss spectroscopy, scanning Auger microanalysis, and proton, ion, and laser microprobe analysis) may provide important complementary information and help overcome some of the limitations of electron probe X-ray microanalysis. Despite differences in physical principles and instrumentation, the various microanalytical methods have much in common with regard to specimen preparation, quantitative analysis, and interpretation of analytical data. A common approach to microanalytical problems in the biological sciences, irrespective of the analytical techniques used, seems therefore indicated.

Electron Probe Microanalysis

Clinical pathology: preanalytical variation in preclinical safety assessment studies--effect on predictive value of analyte tests.

Significant differences in concentrations of analytes in samples may be introduced before samples enter analyzers. These differences are known as preanalytical variation and are part of the overall variation in analytical data. Preanalytical variation is caused by factors that operate during animal preparation prior to sampling, sample collection, sample processing, and sample storage prior to measurement. Preanalytical variation is important because it detracts from the predictive value of analyte measurements. Preanalytical variation may permanently damage data. Because its effects are difficult to quantitate it should be minimized in safety assessment studies. Sources of preanalytical variation are actions performed on animals prior to sample collection and actions performed on the specimen prior to analysis. Preanalytical variation produces a range of artefacts in experimental data. Consequences of preanalytical variation are loss of confidence in the data, obfuscation of real test article effects, false effects, and possibly the expense of repeating a study. To limit preanalytical variation, its sources must be identified, the effects documented, and measures devised to eliminate its sources. Predictive value (likelihood of actual disease) of appropriate clinical pathology tests in toxicology is inversely dependent on preanalytical variation: uncontrolled variation produces data with low predictive values, and controlled variation produces data with high predictive values.

Animals

Evaluation of sequencing reads at scale using rdeval.

MOTIVATION: Large sequencing datasets are being produced and deposited into public archives at unprecedented rates. The availability of tools that can reliably and efficiently generate and store sequencing read summary statistics has become critical. RESULTS: As part of the effort by the Vertebrate Genomes Project (VGP) to generate high-quality reference genomes at scale, we sought to address the community's need for efficient sequence data evaluation by developing rdeval, a standalone tool to quickly compute and interactively display sequencing read metrics. Rdeval can either run on the fly or store key sequence data metrics in tiny read 'snapshot' files. Statistics can then be efficiently recalled from snapshots for additional processing. Rdeval can convert fa*[.gz] files to and from other popular formats including BAM and CRAM for better compression. Overall, while CRAM achieves the best compression, the gain compared to BAM is marginal, and BAM achieves the best compromise between data compression and access speed. Rdeval also generates a detailed visual report with multiple data analytics that can be exported in various formats. We showcase rdeval's functionalities using long-read data from different sequencing platforms and species, including human. For PacBio long-read sequencing, our analysis shows dramatic improvements in both read length and quality over time, as well as the benefit of increased coverage for genome assembly, though the magnitude varies by taxa. AVAILABILITY AND IMPLEMENTATION: Rdeval is implemented in C++ for data processing and in R for data visualization. Precompiled releases (Linux, MacOS, Windows) and commented source code for rdeval are available under MIT license at https://github.com/vgl-hub/rdeval. Documentation is available on ReadTheDocs (https://rdeval-documentation.readthedocs.io). Rdeval is also available in Bioconda and in Galaxy (https://usegalaxy.org). An automated test workflow ensures the consistency of software updates.

Software

Genetic changes across language boundaries in Europe.

By means of three different methods we investigated whether 59 allele frequencies and ten cranial variables show increased change at 29 language-family boundaries in Europe. The quadrat-variance method compares variances of map quadrats crossed by language-family boundaries to variances of quadrats that are not crossed. The rate-of-change method examines the directional derivative of surfaces of the variables perpendicular to a language-family boundary and compares these derivatives to the same quantities obtained by randomly placing the language boundaries on the map of Europe. The difference method tests whether these variables differ more across language-family boundaries than across randomly placed boundaries. These special data-analytic techniques had to be developed to avoid the problem of spatial autocorrelation of both language and biological data. All three methods indicate increased genetic change at language-family boundaries. Clearer and more pronounced results are obtained by the first two methods than by the difference method. Thirteen language-family boundaries show significant gene frequency change by at least one of the methods. Changes are more marked in gene frequencies than in cranial variables. Different allele frequencies mark the increased change at different language boundaries. A model, based on the known history of each language-family boundary, was constructed to predict whether given boundaries should exhibit increased genetic change. The model is in good agreement with the observed results.

Alleles

[LATINFOODS].

Food Composition Tables should be considered as national wealth and as valuable tools for utilization in food and nutrition, in nutritional therapy, in agricultural planning and production, in food guides, and in the food industry for the formulation of information on the product that appears in the label. They should, therefore, be considered as national wealth because they chemically describe the food resources of a country at a very high price, and are considered valuable tools due to their multiple applications. The countries present Tables were published between 1935 and 1961, with analytical data available at that time. So far the Tables have met their purpose, but due to changes that have occurred in raw materials, in analytical methodology, in the new knowledge acquired in nutrition, and in the relationships between food and diseases, in November 1986, representative groups of the Latin American and the Caribbean countries decided to create LATINFOODS. The objective of the program is to promote the development of data banks of foods of the Latin American countries, creating national multidisciplinary groups interested in data production, compilement, publication and utilization, and that eventually, may be homogeneously united to form a data bank for Latin America and the Caribbean Region. During the meeting in favor of the creation of LATINFOODS, detection was made of the constraints of the Food Composition Tables now used as well as the measures needed to correct such problems. These included the number of samples collected as well as the analytical methods used, and the number of nutrients. Due to the observed increase in production and distribution of new food products by the food industry, and to the increased association between foods and diseases, the food industry must participate not only in the generation of data, but in their utilization for food identification, nutrient contribution and nutritional education. Likewise, academic programs in Food Technology should extend the concepts of Food Science with special emphasis on food nutrient contents, to reach an adequate nutritional and health status for the Latin American population.

Databases, Factual

Validity of calculating fatty acid intake from mixed diets.

One hundred and seventy six weighed duplicate diets were collected over 16 consecutive days from 11 subjects. Analyses of their fatty acid composition were used to asses the validity of food composition tables. Four different calculating techniques were employed. Using the published data produced correlation coefficients of 0.29 between analysed and calculated polyunsaturated/saturated fatty acid ratios, whilst the addition of new analytical data and recoding fried foods produced a correlation coefficient of 0.56. The latter method also decreased the mean difference between analysed and calculated polyunsaturated/saturated consumption, when compared with the standard procedure.

Adult

Analytical characterization of isoheroin.

The synthesis of isoheroin is presented with the analytical data (mass spectroscopy [MS], nuclear magnetic resonance [NMR], infrared spectroscopy [IR], and gas liquid chromatography [GLC]) for this compound. Comparison between analytical results for heroin and isoheroin shows differentiation is possible.

Chemical Phenomena

[Evaluation of the information provided by the system of compulsory notification of diseases].

In order to assess activities of epidemiological surveillance resulting from the statutory notification system, a total of 17,394 notification records of eight infectious diseases (brucellosis, bacillary dysentery, typhoid fever, viral hepatitis, meningococcal infection, rickettsioses other than exanthematous typhus, pulmonary tuberculosis, and tuberculosis of other organs) together with 10,503 epidemiological surveys submitted to the "Servei Territorial de Salut Pública" of the province of Barcelona between 1982 and 1986 were reviewed. In notification records, data to locate physicians were the most commonly found (between 92.6% and 99.4% according to disease), whereas in epidemiological surveys, clinical and analytical data were the most frequently encountered. The inclusion of data of epidemiological interest ranged from 3.6 to 68.6%. In order to improve efficacy of the statutory notification system a proposal is made to reduce the extension of epidemiological surveys in terms of requesting only necessary data to establish appropriate measures in each case.

Communicable Disease Control

Thomas: building Bayesian statistical expert systems to aid in clinical decision making.

Knowledge-based system for classical statistical analysis must separate the task of analyzing data from that of using the results of the analysis. In contrast, a Bayesian framework for building biostatistical expert system allows for the integration of the data-analytic and decision-making tasks. The architecture of such a framework entails enabling the system (1) to make its recommendations on decision-analytic grounds; (2) to construct statistical models dynamically; (3) to update a statistical model based on the user's prior beliefs and on data from, the methodological concerns evinced by, the study. This architecture permits the knowledge engineer to represent a variety of types of statistical and domain knowledge. Construction of such systems requires that the knowledge engineer reinterpret traditional statistical concerns, such as by replacing the notion of statistical significance with that of a pragmatic clinical threshold. The clinical user of such a system can interact with the system at a semantic level appropriate to her fund of methodological knowledge, rather than at the level of statistical details. We demonstrate these issues with a prototype system called THOMAS which helps a physician decision maker interpret the results of a published randomized clinical trial.

Artificial Intelligence

The tocopherol, tocotrienol, and vitamin E content of the average Finnish diet.

The Finns average intake of tocopherols, tocotrienols, and vitamin E (alpha-tocopherol equivalents) was determined. The food consumption data were derived mainly from the national food balance sheets (for 1987). The average Finnish daily diet was composed and analyzed both in spring and in autumn in order to minimize the effect of seasonal variation. The four tocopherols and four tocotrienols were then determined using high-performance liquid chromatography (HPLC). For comparison, the intake of vitamin E compounds was also calculated using the most recent Finnish analytical data on tocopherols and tocotrienols in food. According to the analytical results, the average daily vitamin E intake in Finland was 10.7 mg alpha-tocopherol equivalents (alpha-TE) of which amount 85% is due to alpha-tocopherol. The analyzed values (10.8 mg alpha-TE in spring and 10.7 mg alpha-TE in autumn) of vitamin E intake did not markedly differ from the calculated value (10.3 mg alpha-TE), thus indicating that the Finnish food composition data upon tocopherols and tocotrienols is up-to-date and accurate. The best food sources of vitamin E were dietary fat (41% of the total amount), cereals (18%), and dairy products and eggs (13%). The average Finnish diet contained 9.5 g of polyunsaturated fatty acids (PUFA), which leads to the ratio of 0.9 between alpha-tocopherol (mg) and PUFA (g). According to these results, the dietary recommendations for vitamin E are met in Finland.

Antioxidants

A pattern classification system for automated cervical cytologic screening based on flow microfluorometric analysis.

A data analytic technique is described for use in automated cervical cytology. The method entails the application of a two-dimensional Fourier transform to histogram data obtained by flow microfluorometry and the subsequent use of the Fourier coefficients as parameters for pattern classification. Analyses were performed on 186 samples including material from 62 positive and 124 negative cases. Cell suspensions were stained with propidium iodide and fluorescein isothiocyanate, and red and green cytofluoresence were measured simultaneously. The two-dimensional histogram data were normalized, the Fourier transform was applied, and a multivariate classifier based on 30 coefficients was assembled using a training set of half the original series. Performance was then assessed on the remaining cases. Overall accuracy was 79.6%, with a false-positive rate of 14.8% and a false-negative rate of 31.2%. The potential applicability of this approach as the basis of a practical screening system is discussed.

Adolescent

[Problems with standardization of the radioimmunologic determination].

Radioimmunoassay is an analytical procedure in which a radioactive tracer acts as an indicator and a specific antibody acts as a reagent. The requirements which have to be met to guarantee the validity of the assay are the essential characteristics of each microanalytical procedure, namely the sensitivity, specificity, precision and accuracy. The optimization of the assay demands than a careful examination of these factors, which first depend on the properties of the reagents. The consistency of the results is based on the identity, as far as the immunoreactivity is concerned, between the substance to be assayed in the biological sample and the substance used as a standard to build up the calibration curve. The immunoreactivity of the tracer can instead be lower than that shown by the standard, although it must not be too different. The features of all the reagents are reviewed and discussed, mainly those of the antiserum which affect the specificity of the assay. The most diffuse RIA techniques are reviewed and divided in gross categories, according to the methods used for the separation of the free and antibody-bound hormone. The different steps of the analytical procedure are investigated, taking into consideration the most important parameters which affect the assay, mainly the time and temperature of the incubation step. The practical ease of the analysis is definitely an essential factor of choice, provided that it could be associated to reproducible and accurate results. A severe quality control of each reagent and of the assembled set must be carried out to assure the consistency of the analytical data. In the particular case of radioimmunoassay the quality control must be extended to all the steps of the assay both before and after the analytical procedure itself, in order to assure the maximal clinical validity of the diagnostic determination.

Aldosterone

Cardiac function and Fourier phase data from simulated Wolff-Parkinson-White syndrome in a baboon model.

The diagnostic value of Fourier phase analysis and planar scintigraphy in Wolff-Parkinson-White (WPW) syndrome has been suspect. This study investigates phase analytical data from planar radionuclide ventriculography of six baboons with simulated WPW syndrome by means of implanted electrodes. An electrode in the atrium controlled the heart rate and a subsequent stimulation was delivered by electrodes placed at different sites on the ventricles, delayed to cause the characteristic delta wave of the WPW syndrome. Sensitivity for accurately-localizing variously-situated first points of activation (FPAs) from the Fourier phase images was found highest for premature right ventricular (RV) activation, and for atrioventricular (AV) delays around 125 msec. Other sites were subject to artifacts. Changes in cardiac function, phase delay, and histogram parameters were not statistically meaningful.

Animals

Quantitative methods for assessing a synergistic or potentiated genotoxic response.

The problem of assessing chemical interactions in studies of genotoxicity is discussed. Attention is focused on assessing possible synergism or potentiation when the observed genotoxic response is binary (yes-no). Different forms of enhancement are distinguished based upon different assumptions on the genotoxic activity of the experimental treatments. A generalized linear statistical model is considered that links the probability of the binary response to the doses, and data-analytic strategies are described for detecting synergy and potentiation in factorially designed experiments. This approach is illustrated with a series of analyses of various genotoxicity data-sets.

Aminacrine

Quality assurance in pathology. Cytologic and histologic correlation.

In this study we used a computerized program to compare the cytologic and histologic diagnoses made in a three-year period with the aim of evaluating the data obtained as an index of the diagnostic accuracy of cytology in a pathology quality assurance program. Concordance between the cytologic and histologic diagnoses was observed in 83.2% of the cases. In 1.2% the cytologic diagnosis was suspected malignancy, and 78.4% of these cases were positive for tumor at histologic examination. Analysis of the data must be performed in accordance with the anatomic site involved, and discordance must be investigated by a pathologist, especially in view of the different modalities of cytologic and histologic sampling. Analytic data on the breast, bladder and lung are presented.

Cell Biology

A study of the effects of trend, variability, frequency, and form of data on teachers' judgments about progress and their decisions about program change.

Past research has demonstrated the influence of various factors on teachers' judgments about their students' progress. When graphed data are viewed, teachers tend to make different decisions depending upon the amount of data viewed and its trend. Current surveys of teachers' practices in data collection and decision-making indicate that teachers primarily collect training data which are examined in both graphed and ungraphed (response by response) forms to make weekly decisions about progress. In this study, 56 teachers of students with moderate to profound disabilities viewed task analytic data in one of three forms: graphed, ungraphed, or both forms. Teachers were asked to describe the progress and make a program recommendation for each student whose data they examined. Three repeated factors (trend, variability, and frequency of data collection) also were examined for their effect on the dependent variables and their interactions with data form and with each other. Results were in agreement with earlier research and further indicated that the form of the data did not produce different judgments or decisions. However, the three factors, trend, variability, and the frequency of data collection, all had significant main effects with teachers' descriptions about student progress and their program recommendations; several significant interactions among the factors also were found.

Achievement

Exploring simple independent action in multifactor tables of proportions.

The problem of assessing synergistic or antagonistic departure from simple independent action in multifactor tables of proportions is discussed. A generalized linear model is employed in which additivity corresponds to simple independent action. Data-analytic strategies are proposed for exploring departures from simple independent action in various extensions of the 2 X 2 table of proportions. This methodology is illustrated with a series of models fitted to cellular differentiation and murine toxicity data.

Animals

Dietary fat and cancer: consistency of the epidemiologic data, and disease prevention that may follow from a practical reduction in fat consumption.

International variations and national time trends in disease rates suggest major associations between dietary fat and several important cancers. In contrast, case-control and cohort studies of dietary fat in relation to the same cancers generally report weak associations, or have failed to detect any association with fat intake. This study was undertaken in an attempt to understand the apparent discrepancy between these observations. The results provide an insight into the magnitude of cancer risk reduction that may follow from a practical reduction in dietary fat. Regression analyses of international variations in cancer incidence rates were used to estimate relative risks (RR) as a function of fat intakes for both males and females. These analyses focused on cancers of the breast, colon, rectum, ovary, and endometrium in females, and colon, rectum, and prostate cancers in males. Ages 55-69 and 30-44 were considered in order to compare RR estimates between an older and younger age group, and between post- and pre-menopausal women. Corresponding RR estimates were also calculated, based on the regression of changes in disease rates from the mid-1960s to 1980 on changes in dietary fat, using data from several countries. A strong degree of consistency with the RR estimates from international comparisons was observed. The international regression analyses were also used to project changes in cancer rates among Japanese migrants to the United States. A high level of consistency with the observed disease-rate changes was noted. Similarly, the international data analyses were used to project RRs for the fat intake categories used in specific case-control and cohort studies, while acknowledging measurement error in individual dietary assessment. Although certain exceptions are noted, considerable consistency was found between the aggregate and analytic data results, leaving open the strong possibility that a practical reduction in dietary fat could result in a major reduction in the incidence of several prominent cancers in the United States and in other nations having high fat consumption.

Adult